The 31-year-old defender had featured in seven of United's first eight games of the season in all competitions.
However, Maguire suffered a knock in training and was therefore unavailable to manager Erik ten Hag on Sunday.
Maguire still arrived at Old Trafford on Sunday afternoon despite not being fit to play.
Ten Hag selected Matthijs de Ligt and Lisandro Martinez as his starting centre backs, while Victor Lindelof was on the bench for the first time this season.
Maguire, 31, had featured in seven of United's first eight games this season prior to Sunday
Spurs came to Old Trafford without a significant injury absentee of their own after captain Son Heung-min picked up a suspected hamstring issue during Thursday's 3-0 win over Qarabag in the Europa League.
Son was replaced in Tottenham's starting XI by Timo Werner, who was part of a three-man attack with Dominic Solanke and Brennan Johnson.
Spurs boss Ange Postecoglou also named an attack-minded midfield three of Dejan Kulusevski, Rodrigo Bentancur and James Maddison.
Kobbie Mainoo and Manuel Ugarte started at the base of the United midfield.
United and Spurs both went into Sunday's game with seven points from their first five Premier League fixtures.